Evidence map›Paper›PMID 22809691›Full record

ArticlePain2012

Activation of TRPA1 on dural afferents: a potential mechanism of headache pain.

Rebecca M Edelmayer, Larry N Le, Jin Yan, Xiaomei Wei, Romina Nassini, Serena Materazzi, Delia Preti, Giovanni Appendino, Pierangelo Geppetti, David W Dodick and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 3 pooled it
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 3 syntheses or guidelines pooled it, 132 citations in OpenAlex.

  1. Pooled it
  2. Mechanosensitive receptors in migraine: a systematic review.The journal of headache and pain · 2024
    Pooled it
  3. Pooled it
  4. Article
  5. Fragrance-Free Policies: A Scoping Review of Definitions, Implementation, and Gaps.International journal of environmental research and public health · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Laryngeal and Global Somatosensation in Primary Muscle Tension Dysphonia.Journal of voice : official journal of the Voice Foundation · 2024
    Article
  17. TRPA1, TRPV1, and Caffeine: Pain and Analgesia.International journal of molecular sciences · 2024
    Review
  18. Article
  19. Review
  20. Article

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Rebecca M EdelmayerDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA Department of Preclinical and Clinical Pharmacology and Headache Center, University of Florence, Florence, Italy Department of Pharmaceutical Chemistry, University of Ferrara, Ferrara, Italy Department of Chemical, Alimentary, Pharmaceutical and Pharmacological Sciences, University of Eastern Piedmont, Novara, Italy Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Larry N Le
Jin Yan
Xiaomei Wei
Romina Nassini
Serena Materazzi
Delia Preti
Giovanni Appendino
Pierangelo Geppetti
David W Dodick
Todd W Vanderah
Frank Porreca
Gregory Dussor
University of Arizona · USUniversity of Florence · ITMayo Clinic in Arizona · USUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversity of Ferrara · IT

Funding

The Role of ASICs in Migraine PathophysiologyR01NS072204 · NINDS · UNIVERSITY OF TEXAS DALLAS · PI DUSSOR, GREGORY O · 2011 to 2015
$1.9M
NINDS NIH HHS NS072204NINDS NIH HHS R01 NS072204
6 · The paper itself

Abstract

Activation of transient receptor potential ankyrin-1 (TRPA1) on meningeal nerve endings has been suggested to contribute to environmental irritant-induced headache, but this channel may also contribute to other forms of headache, such as migraine. The preclinical studies described here examined functional expression of TRPA1 on dural afferents and investigated whether activation of TRPA1 contributes to headache-like behaviors. Whole-cell patch-clamp recordings were performed in vitro with 2 TRPA1 agonists, mustard oil (MO), and the environmental irritant umbellulone (UMB) on dural-projecting trigeminal ganglion neurons. Application of MO and UMB to dural afferents produced TRPA1-like currents in approximately 42% and 38% of cells, respectively. By means of an established in vivo behavioral model of migraine-related allodynia, dural application of MO and UMB produced robust time-related tactile facial and hind paw allodynia that was attenuated by pretreatment with the TRPA1 antagonist HC-030031. Additionally, MO or UMB were applied to the dura, and exploratory activity was monitored for 30min with an automated open-field activity chamber. Dural MO and UMB decreased the number of vertical rearing episodes and the time spent rearing in comparison to vehicle-treated animals. This change in activity was prevented in rats pretreated with HC-030031 as well as sumatriptan, a clinically effective antimigraine agent. These data indicate that TRPA1 is expressed on a substantial fraction of dural afferents, and activation of meningeal TRPA1 produces behaviors consistent with those observed in patients during migraine attacks. Further, they suggest that activation of meningeal TRPA1 via endogenous or exogenous mechanisms can lead to afferent signaling and headache.

Indexed as

AnimalsDura MaterHeadacheIn Vitro TechniquesIrritantsMaleMonoterpenesMustard PlantNeurons, AfferentPatch-Clamp TechniquesPlant OilsRatsRats, Sprague-DawleyTrigeminal GanglionTRPA1 Cation ChannelTRPC Cation Channels(1R,5S)-4-methyl-1-propan-2-ylbicyclo(3.1.0)hex-3-en-2-oneIrritantsMonoterpenesmustard oilPlant OilsTRPA1 Cation ChannelTrpa1 protein, ratTRPC Cation Channels

Identifiers

PMID22809691
PMCPMC3413768
OpenAlexW2088981463

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.